Study of an Individualized Vaccine Targeting Neoantigens in Combination With Immune Checkpoint Blockade for Patients With Colon Cancer

NCT05456165 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: GO-008GRANITE-ADJUVANT
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objective is to assess and characterize the antitumor activity and safety and tolerability of adjuvant treatment with an individualized neoantigen vaccine called GRT-C901/GRT-R902 (chimpanzee adenovirus \[ChAd\] and self-amplifying messenger RNA \[samRNA\] vectors), in combination with checkpoint inhibitors. Antitumor activity will be based on molecular response in patients with colon cancer who have circulating tumor deoxyribonucleic acid (ctDNA) following surgical resection.

Conditions

Colonic Neoplasms; Colorectal Neoplasms

Outcome Measures

Primary Outcomes (2)

• Percentage of Patients with a ≥50% Decrease from Baseline in Circulating Tumor deoxyribonucleic acid (ctDNA)

  Baseline and up to ~24 months

• Incidence and Severity of Adverse Events

  The incidence and severity will be assessed for treatment-emergent adverse events (TEAEs), immune-related AEs (irAEs), treatment-related AEs, serious AEs (SAEs), AEs leading to death while patients are on treatment or up to 100 days after the last study treatment, AEs leading to dose delays or dose discontinuation, and AEs leading to discontinuation of study treatment using National Cancer Institute (NCI) Criteria for Adverse Events (CTCAE) v5.0

  Up to ~100 days after last study treatment (Up to 62 weeks)

Secondary Outcomes (7)

• Recurrence-free survival (RFS) per Investigator

  From time of randomization until first recurrence of the same cancer, or death (Up to ~36 months)

• Disease-free survival (DFS) per Investigator

  From time of randomization until first recurrence of any cancer, or death (Up to ~36 months)

• Overall Survival (OS)

  From time of randomization until death due to any cause (Up to ~36 months)

• Conversion of Patients with ctDNA at Baseline to Undetectable ctDNA as Assessed via a Polymerase Chain Reaction (PCR)-Based Assay

  Baseline and up to ~24 months

• Longest Duration of Molecular response of ctDNA Decrease from Baseline

  Baseline and up to ~24 months

Study Arms (2)

GRT-C901/GRT-R902 Vaccine arm

EXPERIMENTAL

After surgical resection, patients who are circulating tumor DNA (ctDNA) positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction, randomization, and vaccine manufacturing. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will receive a total of 6 doses of GRT-C901/ GRT-R902, 2 doses of ipilimumab, and 13 doses of atezolizumab. Study visits occur every 28 days.

Drug: GRT-C901; Drug: GRT-R902; Drug: Atezolizumab; Drug: Ipilimumab; Drug: Adjuvant chemotherapy

Observation arm

ACTIVE COMPARATOR

After surgical resection, patients who are ctDNA positive will receive adjuvant chemotherapy for 12-24 weeks during which they will undergo neoantigen prediction and randomization. After study treatment screening, patients who are still ctDNA positive with no evidence of residual or metastatic disease will be observed via study visits occur every 12 weeks.

Drug: Adjuvant chemotherapy

Interventions

GRT-C901 DRUG

An individualized neoantigen cancer vaccine using an adenovirus vector administered via intramuscular (IM) injections at Visit 1 and boost at Visit 6.

GRT-C901/GRT-R902 Vaccine arm

GRT-R902 DRUG

An individualized neoantigen cancer vaccine using a self-amplifying mRNA (samRNA) vector administered via IM injection at Visits 2, 4, 9, and 12.

GRT-C901/GRT-R902 Vaccine arm

Atezolizumab DRUG

Dose of 1680 mg administered once every 4 weeks (Q4W) via intravenous (IV) infusion at Visits 1-13.

GRT-C901/GRT-R902 Vaccine arm

Ipilimumab DRUG

Dose of 30 mg administered via subcutaneous (SC) injection only with the first dose of GRT-C901 at Visit 1 and GRTR902 at Visit 2.

GRT-C901/GRT-R902 Vaccine arm

Adjuvant chemotherapy DRUG

Administered according to standard of care.

GRT-C901/GRT-R902 Vaccine arm; Observation arm

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• For Vaccine Production Stage:
• Patients with a high-risk stage II or stage III colon cancer, including high-risk stage II colon cancer defined as meeting any of the following criteria: T4 tumors, Grade ≥3, clinical presentation with bowel obstruction or perforation, histological signs of vascular or lymphatic or perineural invasions, and \<12 nodes examined
• Patient has evidence of minimal residual disease (MRD) prior to initiating adjuvant chemotherapy (ACT) based on the presence of ctDNA
• Patient has received approximately \<6 weeks of ACT.
• Margin negative (R0) pathology on resection
• Availability of formalin fixed, paraffin embedded (FFPE) tumor specimens
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 or equivalent for patients 12 to 17 years of age
• Patient has adequate organ function as defined by: peripheral white blood cell (WBC) count ≥3000/mm\^3, absolute lymphocyte count (ALC) ≥800/mm\^3, absolute neutrophils count (ANC) ≥1500/mm\^3, platelets ≥100,000/mm\^3, hemoglobin ≥9 g/dL, albumin ≥3 g/dL, calculated creatinine clearance \>50 mL/min using Cockcroft-Gault equation, alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤3 × upper limit of normal (ULN), total serum bilirubin ≤1.5 × ULN OR direct bilirubin ≤1 × ULN, international normalized ratio (INR), prothrombin time (PT), or partial thromboplastin time (PTT) ≤1.5 × ULN, unless patient is receiving anti-coagulant therapy, in which case patients are eligible if PT and PTT are within therapeutic range of intended use of anti-coagulants, and carcinoembryonic antigen levels ≤1.5 × ULN.
• A woman of childbearing potential (WCBP) must be willing to undergo pregnancy testing and agrees to the use at least 1 highly effective contraceptive method during the study treatment period and for 5 months after last investigational study treatment
• For Study Treatment Stage:
• Have a confirmed diagnosis of high-risk stage II or stage III micro-satellite stable (MSS)-colon cancer and have had their tumor surgically resected, have completed standard ACT and have no evidence of disease radiographically, and have evidence of MRD based on detection of ctDNA following ACT
• ECOG performance status of 0 to 1 or equivalent for patients 12-17 years of age
• Have adequate organ function with peripheral WBC count ≥2000/mm\^3, ALC ≥500/mm\^3, ANC ≥1000/mm\^3, platelets ≥75,000/mm\^3, hemoglobin ≥9 g/dL, albumin ≥3 g/dL, calculated creatinine clearance \>40 mL/min using Cockcroft-Gault equation, ALT and AST ≤3 × ULN, total serum bilirubin ≤1.5 × ULN OR direct bilirubin ≤1 × ULN, and INR, PT, or PTT ≤1.5 × ULN
• If a WCBP, must be willing to undergo pregnancy testing and agrees to the use at least 1 highly effective contraceptive method during the study treatment period and for 5 months after last investigational study treatment
• If male and sexually active with a WCBP, must agree to use highly effective contraception such as latex condom plus partner use of a highly effective contraceptive method during the study treatment period and for 5 months after last investigational study treatment.

You may not qualify if:

• For Vaccine Production Stage:
• Patients with micro-satellite instable (MSI)-high disease
• Patients with known tumor mutational burden (TMB) \<1 non-synonymous mutations/megabase
• Patients with known DNA Polymerase Epsilon mutations
• Known exposure to chimpanzee adenovirus (ChAd) within the prior 6 months, plan to receive a ChAd-based vaccine in the next 6 months, and/or any history or anaphylaxis in reaction to a vaccination
• Bleeding disorder or history of significant bruising or bleeding following intramuscular (IM) injections or blood draws
• Immunosuppression anticipated at time of study treatment
• Patient has received prior therapy consisting of anti-cytotoxic T lymphocyte-associated antigen (CTLA-4), anti-programmed cell death-1 receptor (PD-1), anti-programmed death ligand-1(PD-L1), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• History of allogeneic tissue/solid organ transplant
• Active or history of autoimmune disease or immune deficiency
• History of other cancer within 2 years
• Active tuberculosis or recent (\<2 week) clinically significant infection, or evidence of active hepatitis B or hepatitis C or known history of positive test for human immunodeficiency virus (HIV) if CD4+ T-cell count is ≤200 cells/microliter.
• History of pneumonitis requiring systemic steroids for treatment (with the exception of prior resolved in-field radiation pneumonitis)
• Myocardial infarction within 3 months or prior to study treatment, unstable angina, serious uncontrolled cardiac arrhythmia, history of myocarditis, or congestive heart failure (New York Heart Association \[NYHA\] Grade 3 and 4)
• Pregnant, planning to become pregnant, or nursing

Sponsors & Collaborators

• Gritstone bio, Inc.: lead

Study Sites (3)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Christ Hospital Cancer Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms

Interventions

atezolizumab; Ipilimumab; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2022
• First Posted: July 13, 2022
• Study Start: May 19, 2022
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: December 31, 2024

Record last verified: 2024-12

Locations

US (3)